This invention relates to nuclear magnetic resonance spectrometers. More particularly, this invention relates to the upper stack of a nuclear magnetic resonance spectrometer. This invention also relates to a method for operating a nuclear magnetic resonance spectrometer apparatus.
NMR has many advantages, including its universal applicability as a non-destructive tool for analysis of compounds containing suitable magnetic nuclei, the near quantitative relationship between resonance intensity and molecular abundance, and the sensitivity of NMR observables to molecular structure. NMR suffers severely, however, from limited sensitivity.
A number of methods have been introduced over the years for enhancement of NMR sensitivity in selected applications. These include CIDNP (chemically induced dynamic nuclear polarization), polarization through reaction with para hydrogen, optically detected NMR, transfer from optically pumped Xe or He, and microwave induced DNP (dynamic nuclear polarization). DNP has recently developed to the point of commercialization. It relies on transfer of polarization from electron spins to nuclear spins using either three spin solid-state mechanisms or thermal mixing. The polarization for electrons is a factor of 650 larger than for protons and a factor of 2600 larger for carbon-13 when compared at similar temperatures and magnetic fields. Some very spectacular results have been reported, including enhancements of factors of several thousand for carbon-13. There are results for nitrogen-15 that are even more impressive. However, there are disadvantages to DNP, both in general, and as specifically implemented in current commercial designs. First, DNP requires addition of a free radical species at a concentration adequate to yield efficient polarization in the solid state. Partly because of the spin relaxation contributions of the free radical, applications have been largely limited to observations of 13C even though the ultimate sensitivity for 1H would be better. Second, DNP requires fairly complex instrumentation with capabilities for both NMR and continuous microwave irradiation at an appropriate frequency. Third, polarization can take a significant length of time even with the best instrumentation. And fourth, some rapid melting procedure is required if solution NMR observation is the objective.
Current commercial instrumentation is based on providing a separate lower field magnet that can use commonly available microwave sources, although some non-commercial ventures have chosen to develop specialized high frequency microwave sources. In the commercial device, transfer of the sample to the observation magnet and melting of the sample is accomplished by flushing the polarization chamber with a large volume of warm solvent (typically 4 ml). This procedure results in undesired dilution of the sample and substantial loss of sensitivity (only 100 μl are used for observation in our highest sensitivity NMR probes). Solvents commonly used for this procedure are also non-aqueous. In addition, the current procedure limits sample polarization to one sample at a time, resulting in preparation of as few as one sample per hour. Similar limitations occur for the other sensitivity enhancement methods (the need for reactive reagents, complex instrumentation, etc). All of these factors suggest that additional options for sensitivity enhancement should be explored. For a subset of important biological applications of NMR, it would be of significant benefit to increase the sensitivity of NMR techniques, even by as little as an order of magnitude, if this could be done with simpler apparatus and procedures.